The Role of Fibrin(ogen) in Leukocyte Secretion of Urokinase Plasminogen Activator (uPA) (2013)
Undergraduates: Erin Lewchuk, Maria Aleman
Faculty Advisor: Dr. Alisa Wolberg
Department: Biology
Thrombosis is the inappropriate formation of a blood clot within a blood vessel that obstructs the flow of blood through the circulatory system. Cardiovascular disease, and the associated thrombosis, is the number one killer of Americans today. The clotting cascade results in the activation of a protease, specifically thrombin, which converts fibrinogen to fibrin. Fibrin polymerizes into an insoluble network that forms a clot. Degradation of the clot is mediated by urokinase-type and/or tissue-type plasminogen activators (uPA and tPA respectively). We hypothesize that leukocyte interaction with fibrin increases leukocyte secretion of uPA. Lipopolysaccharide (LPS) stimulated, interleukin-1b (IL1-b) stimulated, and unstimulated human peripheral blood mononuclear cells were incubated for 2 hours at 37 oC in the presence or absence of immobilized fibrinogen. An ELISA was performed to measure the total amount of human uPA antigen present in the cell lysates and supernatants. The data shows a trend towards enhanced secretion of uPA from leukocytes into the supernatant with the presence of fibrinogen and stimulation of the cells. Future experiments include repeating these assays to get a larger N, and using a peptide to disrupt the binding of leukocytes to fibrin via the major leukocyte receptor for fibrin (the MAC-1 receptor).